Stem cells obtained from adults (mesenchymal, hematopoietic, neuronal) are receiving increasing interest as a source of material for cell and tissue transplantation to treat human disease. To a large degree, this interest has been stimulated by findings that report the presence of certain types of stem cells in unexpected tissue compartments in vivo (e.g. neuronal stem cells in bone marrow). In addition, some types of stem cells are displaying an unanticipated plasticity in their ability to trans-differentiate into other types of cells when transplanted from their niche into heterologous tissue compartments. Despite these developments, problems of stem cell accessibility and quantity persist.
The transdifferentiation potential of adult cells has also been receiving increasing attention during the past few years (Eguchi and Kodama, 1993). Trans-differentiation is a physiological process that occurs during development but has also been described in a number of adult organs including liver, thyroid, mammary gland (Hay and Zuk, 1999), and kidney (Strutz et al., 1995). It has been shown that alteration of cell morphology and function can be induced artificially in vitro by treatment of cell cultures with cytoskeletal disruptors, hormones, and Calcium-ionophores. Trans-differentiation is a physiological process that occurs during development, and has also been described in a number of adult organs including liver, thyroid, mammary gland (Hay and Zuk, 1999), and kidney (Ng et al., 1999). Alteration of cell fate can be induced artificially in vitro and there is a vast amount of published data describing trans-differentiation. For example, embryonic blastomeres can be induced to differentiate in the presence of microfilament inhibitors (Okado and Takahashi, 1988, 1990; Wu et al., 1990; Pratt et al., 1981). Supplementing growth media for somatic cells with cytoskeletal inhibitors (Brown and Benya, 1988; Takigawa et al., 1984; Shea, 1990; Tamai et al., 1999; Cohen et al., 1999; Fernandez-Valle et al., 1997; Yujiri et al., 1999; Ulloa and Avila, 1996; Ferreira et al., 1993; Sato et al., 1991; Zanetti and Solursh, 1984; Kishkina et al., 1983; Hamano and Asofsky, 1984; Holtzer et al., 1975; Cohen et al., 1999), Ca-ionophores (Shea, 1990; Sato et al., 1991), corticosteroids (Yeomans et al., 1976), and DMSO (Hallows and Frank, 1992), causes changes in cell shape and function. Mammary epithelial cells can be induced to acquire muscle-like shape and function (Paterson and Rudland, 1985), spleen cells can be induced to produce both IgM and IgG immunoglobulins (van der Loo et al., 1979), pancreatic exocrine duct cells can acquire insulin-secreting, endocrine, phenotype (Bouwens, 1998a,b), 3T3 cells into adipose cells (Pairault and Lasnier, 1987), mesenchymal cells into chondroblasts (Rosen et al., 1986), bone marrow cells into liver cells (Theise et al., 2000), islets into ductal cells (Yuan et al., 1996), muscle into 7 non-muscle cell types, including digestive, secretory, gland, nerve cells (Schmid and Alder, 1984), muscle into cartilage (Nathanson, 1986), neural cells into muscle (Wright, 1984), bone marrow into neuronal cells (Black, 2000). However, complete conversion to a fully functional and stable different type of cell has never been demonstrated.